Age sensitivity of behavioral tests and brain substrates of normal aging in mice

Abstract

Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

Time–place learning over a lifetime: absence of memory loss in trained old mice

“…The striatum and hippocampus are widely held to be components of distinct memory systems that can guide competing behavioral strategies and compensate for each other in case of temporal or permanent damage (Becker et al 1980;Packard et al 1989;McDonald and White 1993;Berke et al 2009). Multiple behavioral paradigms, like fear conditioning and various maze tasks have different versions which are either more hippocampal-dependent, or more dependent on other memory systems (e.g., striatum, amygdala, cortex) (for review, see Kennard and Woodruff-Pak 2011). A consistent finding in these studies is that the hippocampus-dependent version is more age-sensitive than the nonhippocampus-dependent version.…”

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

“…In line with this, age-dependent reduction in the density of synaptic proteins were reported in the rodent brain, namely SNARE complex proteins, vesicle-mobilizing proteins, vesicular neurotransmitter transporters, postsynaptic proteins, and components of the synaptic vesicle cycle (Canas et al, 2009;VanGuilder et al, 2010), which can contribute to the hippocampal function decline and thus to reduction of memory performance (Allard et al, 2012;Gage et al, 1984a;Kennard and Woodruff-Pak, 2011;Pistell et al, 2012).…”

A Comparative Study Evaluating the Impact of Physical Exercise on Disease Progression in a Mouse Model of Alzheimer’s Disease

“…Here, we used the Y-maze task, which has been validated by our group and others in TgCRND8 mice [24,29,30]. In comparison to the Morris water maze, the Y-maze is less stressful and requires minimal training, thereby minimizing potential confounds of stress hormones and the learning process on outcome measures [31][32][33][34].…”